The present invention relates to an agent for preventing and treating disturbances of intestinal mucous membrane. More particularly, the present invention relates to an agent for preventing and treating disturbances of intestinal mucous membrane, comprising, as the active ingredient, a carbostyril derivative represented by the following general formula (I): ##STR1## (wherein, R is a halogen-atom (a fluorine atom, a chlorine atom, a bromine atom or an iodine atom); the substituent on the carbostyril skeleton is at the 3- or 4-position of the carbostyril skeleton; and the bond between the 3- and 4-positions of the carbostyril skeleton is a single bond or a double bond) or a salt thereof, preferably 2-(4-chlorobenzoylamino)-3-(2-quinolon-4-yl)propionic acid or a salt thereof.
[Prior Art and Problems to Be Solved by the Invention]
The carbostyril derivatives represented by the above general formula (I) and the processes for production of said derivatives are described in Japanese Patent Publication No. 63-35623, etc. and the utility of said derivatives as an inhibitor for gastric ulcer is known. Further, the utility of the derivatives as a gastritis-treating agent is described in Japanese Patent Application Kokai (Laid-Open) No. 3-74329, and the processes for producing those compounds of said derivatives having an optical activity are described in Japanese Patent Application Kokai (Laid-Open) No. 3-145468.
Furthermore, inhibiting effect of compounds of the present invention on reactive oxygen metabolites is described in Japan. J. Pharmacol., Vol. 49, pp. 441-448 (1989), and the gastric mucous membrane protectability of the present invention compounds is described in Folia pharmacol. japon., Vol. 97, pp. 371-380 (1991).
Disturbances of intestinal mucous membrane include simple and primary ulcer of small intestine, nonspecific ulcer of colon, ulcerative colitis induced by nonspecific inflammations, Crohn's disease, etc., all of which appear owing to unknown causes. Disturbances of intestinal mucous membrane also appear owing to known causes such as infections, circular disturbances, collagen disease, radiations, medicines and the like. These disturbances of intestinal mucous membrane are generally hard to cure and, in some cases, surgical treatments are applied thereto. As the medicinal therapy for the disturbances, there are used adrenocortical steroids, Salazopyrin, immunosuppressive agents, etc. However, the steroidal drugs show side effects when administered in a large amount over a long period of time, and the immunosuppressive agents must be carefully used because of the very harmful side effects. Hence, it is desired to develop a medicine which is effective to the treatment of intractable disturbances of intestinal mucous membrane and which can be used safely over a long period of time.
Nonsteroidal anti-inflammatory drugs (hereinafter referred to as NSAID), which are widely used for various diseases attended by inflammations such as arthritis, chronic rheumatoid arthritis and the like, are known to give rise to disturbances of intestinal mucous membrane. The administration of these drugs must therefore be stopped in the middle in some cases. In patients of chronic rheumatoid arthritis, the treatment of rheumatism must be continued even when disturbances of intestinal mucous membrane have appeared, which requires the continued use of NSAID in such cases and poses a problem.
Under such a situation, various attempts were made to administer NSAID without incurring any disturbance of intestinal mucous membrane. For example, it was attempted to use a drug such as Sucralfate, Ranitidine (a histamine H.sub.2 blocker) or the like in combination with NSAID [e.g. Caldwell, J. R., et al., Am. J. Med., Vol. 83, pp. 74-82, 1987, and Ehsanullah, R. S. B. et al., Br. Med. J., Vol. 297, pp. 1017-1021, 1988]. However, no satisfactory result has been obtained yet.